Chiari malformation type I surgery in children: French multicenter 10-year cohort.

OBJECTIVE: Chiari malformation type I (CM-I) is frequent in children and remains a surgical challenge. Several techniques have been described for posterior fossa decompression. No decision algorithm has been validated, and strategies are highly variable between institutions. The goal of this study was to define therapeutic guidelines that take into consideration patient specificities. METHODS: The authors retrospectively collected data from patients who were < 18 years of age, were diagnosed with CM-I, and were treated surgically between 2008 and 2018 in 8 French pediatric neurosurgical centers. Data on clinical features, morphological parameters, and surgical techniques were collected. Clinical outcomes at 3 and 12 months after surgery were assessed by the Chicago Chiari Outcome Scale. The authors used a hierarchical clustering method to define clusters of patients by considering their anatomical similarities, and then compared outcomes between surgical strategies in each of these clusters. RESULTS: Data from 255 patients were collected. The mean age at surgery was 9.6 ± 5.0 years, syringomyelia was reported in 60.2% of patients, the dura mater was opened in 65.0% of patients, and 17.3% of patients underwent a redo surgery for additional treatment. The mean Chicago Chiari Outcome Scale score was 14.4 ± 1.5 at 3 months (n = 211) and 14.6 ± 1.9 at 12 months (n = 157). The hierarchical clustering method identified three subgroups with potentially distinct mechanisms underlying tonsillar herniation: bony compression, basilar invagination, and foramen magnum obstruction. Each cluster matched with specific outcomes. CONCLUSIONS: This French multicenter retrospective cohort study enabled the identification of three subgroups among pediatric patients who underwent surgery for CM-I, each of which was associated with specific outcomes. This morphological classification of patients might help in understanding the underlying mechanisms and providing personalized treatment.

Temporosylvian arachnoid cysts in children. Part 1: Cognitive profile of children with a temporal cyst and impact of the cyst in daily life. A prospective study in 100 consecutive children.

OBJECTIVE: The aim of this study was to determine the cognitive profile of children with a temporal arachnoid cyst (TAC) and its impact on daily life. METHODS: The authors prospectively analyzed the cognitive and psychological profiles of 100 consecutive children relative to age and cyst characteristics (side, cyst size, and cyst shape: convex or nonconvex) and their outcome 4 years later. RESULTS: Mean IQs were normal but with high heterogeneity on Full Scale IQ (FSIQ; range 59-150); 29% of children had at least one Wechsler index below the norm, in particular, Processing Speed and Working Memory Indexes. Impairments were observed in language for 31% of children, as well as in verbal memory (28%), visual memory (23%), executive function (21%), and visual attention (24%). Half of the children (50%) needed rehabilitation for learning difficulties, and 26% had academic difficulties. The parental questionnaire BRIEF (Behavior Rating Inventory of Executive Function) revealed significant executive dysfunctions in daily life for 22% of the children. One-third of the patients (34%) required psychotherapy for anxiety or social disorders, with higher rates in patients with a right-sided cyst and older children. Cyst size had very little neuropsychological impact. Convex cysts were significantly associated with worse performance than nonconvex cysts on all Wechsler indexes and FSIQ, and in language, verbal memory, attention, and visuospatial skills. Children with a convex cyst had significantly more executive and behavior difficulties in daily life and more psychotherapy than other children. The effect of cyst shape was independent of Galassi type and cyst side. Children with a ruptured cyst or an incidentally discovered cyst usually had a good cognitive level. Four years later, children without initial disorders remained stable, whereas those with difficulties who did not undergo surgery needed more rehabilitation and school adaptations. CONCLUSIONS: This large cohort study revealed a varied profile of children with a TAC: at initial assessment, 50% had neuropsychological difficulties and needed rehabilitation and/or psychotherapy for learning or behavior difficulties, and 50% had no difficulties, which may explain the debate about this pathology. Patients with neuropsychological difficulties had a heterogeneous profile with normal intelligence but selective cognitive and/or behavior disorders that may have a long-term impact on their quality of life, particularly those with a right-sided cyst. A neuropsychological evaluation is not always necessary for a cyst discovered incidentally, but early evaluation is essential in patients with academic, learning, or psychological disorders. When assessment shows selective disorders presumably linked to cyst location, surgery may be considered, particularly for convex cysts, as this study revealed more effects in association with cyst shape than with cyst size and significantly poorer performance with a convex cyst.

In utero treatment of myelomeningocele with allogenic umbilical cord-derived mesenchymal stromal cells in an ovine model.

PURPOSE OF THE STUDY: The purpose of our study was to investigate the effects of ovine umbilical cord-derived mesenchymal stromal cells (UC-MSCs) seeded in a fibrin patch as an adjuvant therapy for fetal myelomeningocele repair in the ovine model. MATERIALS AND METHODS: MMC defects were surgically created at 75 days of gestation and repaired 15 days later with UC-MSCs patch or an acellular patch. At birth, motor function, tail movements, and voiding abilities were recorded. Histological and immunohistochemical analysis included study of MMC defect's healing, spinal cord, UC-MSCs survival, and screening for tumors. RESULTS: Six lambs were born alive in each group. There was no difference between the two groups on the median sheep locomotor rating score but all lambs in the control group had a score between lower than 3 compared to 50% in UC-MSCs group. There were more lambs with tail movements and voiding ability in UC-MSCs group (83% vs 0% and 50% vs 0%, respectively). gray matter area and large neurons density were higher in UC-MSCs group (2.5 vs 0.8 mm2 and 19.3 vs 1.6 neurons/mm2 of gray matter, respectively). Fibrosis thickness at the myelomeningocele scar level was reduced in UC-MSCs group (1269 µm vs 2624 µm). No tumors were observed. CONCLUSION: Fetal repair of myelomeningocele using allogenic UC-MSCs patch provides a moderate improvement in neurological functions, gray matter and neuronal preservation and prevented from fibrosis development at the myelomeningocele scar level.

The utility of poly(somno)graphy in evaluating children with Chiari malformation type II before and after surgical intervention: a case series.

BACKGROUND: Children with Chiari Malformation type II (CM-II) have an increased risk of sleep apnoea. The aim of the study was to describe the management of patients with CM-II in relation to sleep apnoea syndrome, clinical symptoms and magnetic resonance imaging (MRI) findings. CASE SERIES PRESENTATION: The paper reports 8 consecutive patients with CM-II followed between September 2013 and April 2017. The prevalence of sleep apnoea syndrome was high with 6 out of 8 patients having mild-to-severe sleep apnoea. Patients with severe sleep apnoea syndrome (3 patients) were treated with upper airway surgery and/or noninvasive ventilation. CONCLUSION: Our findings highlight the importance of respiratory polygraphy in the management of patients with CM-ΙΙ. Poly(somno)graphy is recommended in the follow-up care of children with CM-II.

Intracerebral Gene Therapy in Four Children with Sanfilippo B Syndrome: 5.5-Year Follow-Up Results.

We report the safety (primary endpoint) and efficacy (secondary endpoint) of a novel intracerebral gene therapy at 5.5 years of follow-up in children with Sanfilippo B. An uncontrolled, phase 1/2 clinical trial was performed in four patients aged 20, 26, 30, and 53 months. Treatment consisted of 16 intracerebral and cerebellar deposits of a recombinant adeno-associated viral vector encoding human α-N-acetylglucosaminidase (rAAV2/5-hNAGLU) plus immunosuppression. An intermediate report at 30 months was previously published. Thirty treatment-emergent adverse events were reported between 30 and 66 months after surgery, including three classified as severe with no serious drug reactions. At 5.5 years, NAGLU activity was persistently detected in the lumbar cerebrospinal fluid (18% of unaffected control level). Circulating T cells reacting against NAGLU peptides were present, indicating a lack of acquired tolerance. Patients 2, 3, and 4 showed progressive brain atrophy and neurocognitive evolution that did not differ from untreated Sanfilippo A/B children. Patient 1, enrolled at 20 months of age, had a milder disease with normal brain imaging and a significantly better cognitive outcome than the three other patients and untreated patients, although not equivalent to normal children. After 5.5 years, the primary endpoint of this study was achieved with a good safety profile of the proposed treatment. We have also observed sustained enzyme production in the brain and absence of immunological tolerance. Cognitive benefit was not confirmed in the three oldest patients. Milder disease in the youngest patient supports further investigations of adeno-associated vector-mediated intracerebral gene therapy in Sanfilippo B.

Cell-Mediated Immunity to NAGLU Transgene Following Intracerebral Gene Therapy in Children With Mucopolysaccharidosis Type IIIB Syndrome.

Mucopolysaccharidosis type IIIB syndrome (Sanfilippo disease) is a rare autosomic recessif disorder caused by mutations in the α-N-acetylglucosaminidase (NAGLU) gene coding for a lysosomal enzyme, leading to neurodegeneration and progressive deterioration of cognitive abilities in affected children. To supply the missing enzyme, several recent human gene therapy trials relied on the deposit of adeno-associated virus (AAV) vectors directly into the brain. We reported safety and efficacy of an intracerebral therapy in a phase 1/2 clinical trial (https://clinicaltrials.gov/ct2/show/NCT03300453), with a recombinant AAV serotype 2/5 (rAAV2/5) coding human NAGLU in four children with MPS IIIB syndrome receiving immunosuppression. It was reported that AAV-mediated gene therapies might elicit a strong host immune response resulting in decreased transgene expression. To address this issue, we performed a comprehensive analysis of cellular immunity and cytokine patterns generated against the therapeutic enzyme in the four treated children over 5.5 years of follow-up. We report the emergence of memory and polyfunctional CD4+ and CD8+ T lymphocytes sensitized to the transgene soon after the start of therapy, and appearing in peripheral blood in waves throughout the follow-up. However, this response had no apparent impact on CNS transgene expression, which remained stable 66 months after surgery, possibly a consequence of the long-term immunosuppressive treatment. We also report that gene therapy did not trigger neuroinflammation, evaluated through the expression of cytokines and chemokines in patients' CSF. Milder disease progression in the youngest patient was found associated with low level and less differentiated circulating NAGLU-specific T cells, together with the lack of proinflammatory cytokines in the CSF. Findings in this study support a systematic and comprehensive immunomonitoring approach for understanding the impact immune reactions might have on treatment safety and efficacy of gene therapies.

Sleep-disordered breathing and its management in children with rare skeletal dysplasias.

Sleep-disordered breathing (SDB) is common in patients with skeletal dysplasias. The aim of our study was to analyze SDB and respiratory management in children with rare skeletal dysplasias. We performed a retrospective analysis of patients with spondyloepiphyseal dysplasia congenita (SEDC), metatropic dysplasia (MD), spondyloepimetaphyseal dysplasia (SEMD), acrodysostosis (ADO), geleophysic dysplasia (GD), acromicric dysplasia (AD), and spondylocostal dysplasia (SCD) between April 2014 and October 2020. Polygraphic data, clinical management, and patients' outcome were analyzed. Thirty-one patients were included (8 SEDC, 3 MD, 4 SEMD, 1 ADO, 4 GD, 3 AD, and 8 SCD). Sixteen patients had obstructive sleep apnea (OSA): 11 patients (2 with SEDC, 1 with SEMD, 1 with ADO, 1 with GD, 2 with AD, and 4 with SCD) had mild OSA, 2 (1 SEMD and 1 GD) had moderate OSA, and 3 (1 SEDC, 1 MD, 1 SEMD) had severe OSA. Adenotonsillectomy was performed in one patient with SCD and mild OSA, and at a later age in two other patients with ADO and AD. The two patients with moderate OSA were treated with noninvasive ventilation (NIV) because of nocturnal hypoxemia. The three patients with severe OSA were treated with adenotonsillectomy (1 SEDC), adeno-turbinectomy and continuous positive airway pressure (CPAP; 1 MD), and with NIV (1 SEMD) because of nocturnal hypoventilation. OSA and/or alveolar hypoventilation is common in patients with skeletal dysplasias, underlining the importance of systematic screening for SDB. CPAP and NIV are effective treatments for OSA and nocturnal hypoventilation/hypoxemia.

AAV2/9-mediated silencing of PMP22 prevents the development of pathological features in a rat model of Charcot-Marie-Tooth disease 1 A.

Charcot-Marie-Tooth disease 1 A (CMT1A) results from a duplication of the PMP22 gene in Schwann cells and a deficit of myelination in peripheral nerves. Patients with CMT1A have reduced nerve conduction velocity, muscle wasting, hand and foot deformations and foot drop walking. Here, we evaluate the safety and efficacy of recombinant adeno-associated viral vector serotype 9 (AAV2/9) expressing GFP and shRNAs targeting Pmp22 mRNA in animal models of Charcot-Marie-Tooth disease 1 A. Intra-nerve delivery of AAV2/9 in the sciatic nerve allowed widespread transgene expression in resident myelinating Schwann cells in mice, rats and non-human primates. A bilateral treatment restore expression levels of PMP22 comparable to wild-type conditions, resulting in increased myelination and prevention of motor and sensory impairments over a twelve-months period in a rat model of CMT1A. We observed limited off-target transduction and immune response using the intra-nerve delivery route. A combination of previously characterized human skin biomarkers is able to discriminate between treated and untreated animals, indicating their potential use as part of outcome measures.

Open fetal surgery for myelomeningocele repair in France.

INTRODUCTION: Open fetal myelomeningocele (MMC) surgery is currently the standard of care option for prenatal MMC repair. We described the population referred to our center and reviewed outcome after open fetal MMC repair. MATERIAL AND METHODS: All patients referred to our center for MMC were reviewed from July 2014 to June 2020. For all the patients who underwent fetal MMC repair, surgical details, maternal characteristics and data from the neonatal to the three-years-old evaluations were collected. RESULTS: Among the 126 patients referred to our center, 49.2% were eligible and 27.4% (n = 17) of them underwent fetal MMC repair. Average gestational age at fetal surgery was 24+6 weeks. There was no case of fetal complication and the only maternal complication was one case of transfusion. We recorded 70% of premature rupture of membranes and 47% of premature labor. Average gestational age at delivery was 34+2 weeks and no patient delivered before 30 weeks. There was no case of uterine scar dehiscence or maternal complication during cesarean section. After birth, 59% of the children had a hindbrain herniation reversal. At 1-year-old, 42% were assigned a functional level of one or more better than expected according to the prenatal anatomic level and 25% required a ventriculoperitoneal shunt. At 3-year-old, all the children attended school and 75% were able to walk with orthotics or independently. CONCLUSION: Open fetal surgery enables anatomical repair of the MMC lesion, a potential benefit on cerebral anomalies and motor function, with a low rate of perinatal and maternal complications.

Acute surgical management of children with ruptured brain arteriovenous malformation.

OBJECTIVE: Rupture of brain arteriovenous malformation (AVM) is the main etiology of intracerebral hemorrhage (ICH) in children. Ensuing intracranial hypertension is among the modifiable prognosis factors and sometimes requires emergency hemorrhage evacuation (HE). The authors aimed to analyze variables associated with HE in children with ruptured AVM. METHODS: This study was a single-center retrospective analysis of children treated for ruptured AVM. The authors evaluated the occurrence of HE, its association with other acute surgical procedures (e.g., nidal excision, decompressive hemicraniectomy), and clinical outcome. Variables associated with each intervention were analyzed using univariable and multivariable models. Clinical outcome was assessed at 18 months using the ordinal King's Outcome Scale for Childhood Head Injury. RESULTS: A total of 104 patients were treated for 112 episodes of ruptured AVM between 2002 and 2018. In the 51 children (45.5% of cases) who underwent HE, 37 procedures were performed early (i.e., within 24 hours after initial cerebral imaging) and 14 late. Determinants of HE were a lower initial Glasgow Coma Scale score (adjusted odds ratio [aOR] 0.83, 95% CI 0.71-0.97 per point increase); higher ICH/brain volume ratio (aOR 18.6, 95% CI 13-26.5 per percent increase); superficial AVM location; and the presence of a brain herniation (aOR 3.7, 95% CI 1.3-10.4). Concurrent nidal surgery was acutely performed in 69% of Spetzler-Martin grade I-II ruptured AVMs and in 25% of Spetzler-Martin grade III lesions. Factors associated with nidal surgery were superficial AVMs, late HE, and absent alteration of consciousness at presentation. Only 8 cases required additional surgery due to intracranial hypertension. At 18 months, overall mortality was less than 4%, 58% of patients had a favorable outcome regardless of surgical intervention, and 87% were functioning independently. CONCLUSIONS: HE is a lifesaving procedure performed in approximately half of the children who suffer AVM rupture. The good overall outcome justifies intensive initial management.

Embryonal tumor with multilayered rosettes, C19MC-altered with sarcomatous differentiation: histopathologic and molecular characterization of one case.

Embryonal tumor with multilayered rosettes, constitutes an aggressive and rare pediatric embryonal tumor of the central nervous system characterized by alterations of the C19MC locus at 19q13.12. Embryonal tumors with multilayered rosettes (ETMRs) span a broad histopathological spectrum with primitive neural features and abundant neuropil. Before the molecular definition of this entity, exceptional cases with heterologous differentiation have been evidenced in the literature. Herein, we report the first case of an ETMR featuring a sarcomatous component with proven C19MC alteration in both components by an in situ hybridization analysis. This data supports the hypothesis of a divergent differentiation of tumoral cells in this case.

Forehead Widening in Nonsyndromic Scaphocephaly Operated After 12 Months of Age.

AIM AND SCOPE: Our standard management is to operate isolated sagittal synostosis around 4 months of age because of morphological and cognitive outcomes. However, some patients present late and the likelihood of spontaneous remodeling is low in isolated sagittal craniosynostosis operated on after 12 months of age with a limited technique. The preliminary result of a modified technique for forehead remodeling and subtotal calvarial remodeling in nonsyndromic scaphocephalic children with late presentation is presented. PATIENTS AND METHODS: All patients older than 1 with isolated sagittal synostosis assessed between 2011 and 2015, over 1 year of age at the time of surgery, with available pre and postoperative computed tomography-scans, were retrospectively included into the study. The following parameters were collected: (1) age at surgery, (2) duration of the procedure, (3) surgical technique, (4) fronto-nasal angle before and after surgery and (5) forehead width before and after surgery. RESULTS: Ten patients aged between 15 months and 6 years were retrospectively included. Delayed surgery was due to late presentation or initial parental reluctance. All patients presented with a transversal narrowing of the forehead and an anterior bulge. Mean age at surgery was 28 months and mean follow up was 23 months (1-4 years). Measurements showed significant improvement of both the fronto-nasal angle and the width of the forehead. CONCLUSIONS: Late-presenting scaphocephalic patients operated on after 12 months of age require forehead remodeling to achieve satisfactory aesthetic results. Modified forehead remodeling by splitting the forehead sagittally into 2 symmetrical halves and adding a midline bone strip is a safe and feasible way to widen the forehead. Long term follow-up is needed to assess this modified technique.

Prevention of Neural Tube Defects by Folic Acid Supplementation: A National Population-Based Study.

Folic acid supplementation is recommended for neural tube defect prevention during pregnancy. We conducted an observational, retrospective national registry study to determine the rate of dispensing of periconceptional folic acid after prescription in a sample of French women representative of the general population. Our study population (n = 186,061) was a representative sample of the French population, recorded in the Health Data System database on pharmacy dispensing of medication and mandatory reporting of pregnancy. Between 2006 and 2016, 14.3% of pregnant women had a prescription for folic acid supplementation during the month preceding conception and for the first 12 weeks of pregnancy. Of these prescriptions, 30.9% were issued before the start of pregnancy. This percentage was lower for first pregnancies. The rate of pharmacy dispensing during the preconception period increased progressively from 3.8% to 8.3% between 2006 and 2016. In France, the rate of pharmacy dispensing of periconceptional folic acid after medical prescription is very low and does not follow international recommendations. It seems essential to implement awareness-raising policies targeting the general population and physicians regarding effective periconceptional supplementation, particularly starting in the preconception period. Clarification of international recommendations and fortification of flour could improve the efficacy of folate supplementation at population level.

Endoscopic aqueductal stenting in the management of pediatric hydrocephalus.

OBJECTIVE: Pediatric patients with long-term shunts may experience specific complications related to the segregation of the supra- and infratentorial spaces along with different pressure regimens, leading to either mesencephalic syndromes during shunt dysfunction or isolated fourth ventricle (IFV). An accepted treatment to reestablish normal CSF pathways and reequilibrate the transtentorial pressures is endoscopic aqueductal stenting (EAS) to avoid restenosis. In the present paper, the authors studied children treated with EAS during the last decade for both IFV and obstructive hydrocephalus, evaluated its impact on the course of the disease, and identified prognostic factors for EAS success. METHODS: A noninterventional retrospective study of routinely acquired data was performed, including all hydrocephalic children undergoing EAS between 2011 and 2019 at Hôpital Necker, Paris, France. The following variables were analyzed: etiology of hydrocephalus; number of surgeries before and after stent placement; indication for EAS; type of stent connection (i.e., connected or not to a ventriculoperitoneal shunt); and the stent position. Stent failure was defined as the need to perform further shunt revision. Univariate and multivariate analyses were run to identify factors associated with stent failure. RESULTS: Seventeen patients with a mean age at stent placement of 6 years (SD 6.5 years, range 1 month-18 years) and with a mean follow-up after EAS of 47.5 months (SD 33.7 months, range 5-120 months) were included in the analysis. The etiology of hydrocephalus was as follows: obstructive tumoral (41%), posthemorrhagic (35%), postinfectious (12%), and dysraphism related (12%). The indication for EAS was IFV (47%), rostral midbrain dysfunction syndrome (35%), prevention of secondary aqueductal stenosis after debulking surgery (12%), or primary aqueductal stenosis (6%). No transient or permanent neurological deficits related to the procedure were observed. After EAS, 10 patients did not require further surgeries (59%), and for the others the number of hydrocephalus-related surgeries significantly decreased after stenting. In univariate analysis posthemorrhagic etiology and prevention of aqueductal stenosis were identified as predictors of a good outcome, whereas in multivariate analysis posthemorrhagic hydrocephalus was found to predict a favorable outcome. CONCLUSIONS: The results confirm EAS as a first-line treatment for IFV and suggest its efficacy in changing the history of hydrocephalic patients who have undergone multiple operations and who experience rostral midbrain dysfunction syndrome, as well as efficacy in the prevention of aqueductal stenosis in selected cases of obstructive tumoral hydrocephalus.

Role of neoadjuvant chemotherapy in metastatic medulloblastoma: a comparative study in 92 children.

BACKGROUND: Previous pilot studies have shown the feasibility of preoperative chemotherapy in patients with medulloblastoma, but benefits and risks compared with initial surgery have not been assessed. METHODS: Two therapeutic strategies were retrospectively compared in 92 patients with metastatic medulloblastoma treated at Gustave Roussy between 2002 and 2015: surgery at diagnosis (n = 54, group A) and surgery delayed after carboplatin and etoposide-based neoadjuvant therapy (n = 38, group B). Treatment strategies were similar in both groups. RESULTS: The rate of complete tumor excision was significantly higher in group B than in group A (93.3% vs 57.4%, P = 0.0013). Postoperative complications, chemotherapy-associated side effects, and local progressions were not increased in group B. Neoadjuvant chemotherapy led to a decrease in the primary tumor size in all patients; meanwhile 4/38 patients experienced a distant progression. The histological review of 19 matched tumor pairs (before and after chemotherapy) showed that proliferation was reduced and histological diagnosis feasible and accurate even after neoadjuvant chemotherapy. The 5-year progression-free and overall survival rates were comparable between groups. Comparison of the longitudinal neuropsychological data showed that intellectual outcome tended to be better in group B (the mean predicted intellectual quotient value was 6 points higher throughout the follow-up). CONCLUSION: Preoperative chemotherapy is a safe and efficient strategy for metastatic medulloblastoma. It increases the rate of complete tumor excision and may improve the neuropsychological outcome without jeopardizing survival. KEY POINTS: 1. Preoperative chemotherapy increases the rate of complete tumor removal.2. No additional risk (toxic or disease progression) is linked to the delayed surgery.3. Preoperative chemotherapy could have a positive impact on the neuropsychological outcome of patients.

Spinal dysraphism as a new entity in V.A.C.TE.R.L syndrome, resulting in a novel acronym V.A.C.TE.R.L.S.

Anorectal malformation (ARM) is the most common symptom in VACTERL syndrome (vertebral, anal, cardiac, tracheo-esophageal fistula, renal, and limb anomalies). The association of ARM and spinal dysraphisms (DYS) is well documented. We aim to better evaluate children with VACTERL association and ARM, considering the presence or not of DYS. Between 2000 and 2015, 279 children with VACTERL associations were identified in Necker Children's Hospital, Paris. We identified 61 VACTERL children (22%) with ARM. A total of 52 VACTERL children with ARM were included. DYS were identified in 36/52 of cases (69.2%). A total of 33 (63.5%) VACTERL children presented with sphincterial dysfunction. We constated that 28/33 (84.8%) of them had DYS + (p < 0.0001). More children in ARM (DYS +) subgroup are presenting with initial urinary sphincter dysfunction (58 vs 19%, p < 0.009) than ARM (DYS -). We identified 29 lipoma filum in our series, which were not statistically associated with urinary disorders (p = 0.143).Conclusion: We propose to refine the definition of VACTERL association, by adding S as Spinal defect to include it as an integral part of this syndrome, resulting in a novel acronym V.A.C.TE.R.L.S.What is Known:• The VACTERL association: congenital anomalies of the bony vertebral column (V), anorectal malformation (A), congenital cardiopathy (C), tracheo-esophageal defects (TE), renal and urinary tract anomalies (R), and limb malformations (L).• VACTERL children needs a complete appraisal, as early as possible, to adopt the most appropriate therapeutic management.What is New:• Include spine dysraphism (DYS) as a part of this syndrome, resulting in a novel acronym V.A.C.TE.R.L.S.• The significant correlation between VACTERL/DYS and urinary dysfunction requires to investigate the spine cord prenatally.

High Prevalence of Developmental Venous Anomaly in Diffuse Intrinsic Pontine Gliomas: A Pediatric Control Study.

BACKGROUND: No link has been demonstrated between diffuse intrinsic pontine glioma and developmental venous anomaly in pediatric patients. OBJECTIVE: To determine the prevalence of developmental venous anomaly in a pediatric cohort of diffuse intrinsic pontine glioma. METHODS: We performed a retrospective cohort study (1998-2017) of consecutive pediatric patients harboring a diffuse intrinsic pontine glioma (experimental set, n = 162) or a craniopharyngioma (control set, n = 142) in a tertiary pediatric neurosurgical center. The inclusion criteria were the following: age <18 yr at diagnosis; histopathological diagnosis of diffuse intrinsic pontine glioma or craniopharyngioma according to the 2016 World Health Organization classification of tumors of the central nervous system; no previous oncological treatment; and available preoperative magnetic resonance imaging performed with similar acquisition protocol. RESULTS: We found a significantly higher prevalence of developmental venous anomaly in the experimental set of 162 diffuse intrinsic pontine gliomas (24.1%) than in the control set of 142 craniopharyngiomas (10.6%; P = .001). The prevalence of developmental venous anomalies was not significantly impacted by demographic data (sex, age at diagnosis, and underlying pathological condition), biomolecular analysis (H3-K27M-mutant subgroup, H3.1-K27M-mutant subgroup, and H3.3-K27M-mutant subgroup), or imaging findings (anatomic location, anatomic extension, side, and obstructive hydrocephalus) of the studied diffuse intrinsic pontine gliomas. CONCLUSION: We report a higher prevalence of developmental venous anomaly in pediatric diffuse intrinsic pontine glioma patients than in control patients, which suggests a potential underlying common predisposition or a causal relationship that will require deeper investigations.

Management of Gorham Stout disease with skull-base defects: Case series of six children and literature review.

BACKGROUND: Gorham-Stout disease (GSD) is a rare lymphatic disorder which results in bone destruction. Defects of the skull base are difficult to manage, we describe cases to better understand the disease and discuss treatment. METHODS: Retrospective study including all patients treated for GSD skull-base defects. Medical records, clinical, imaging and treatment data were studied. A systematic review of the literature included case reports of the diseases for further analysis. RESULTS: 6 patients (5 males, 1 female) were included. Mean age at diagnosis was 3.5 years (range 0-10). Follow-up was of 5.2 years. Patients were divided into Naso-temporal (NT) and Vertebro-temporal (VT) groups following anatomical location. NT patients (4 patients) all had petrous defects extending anteriorly, including sphenoid, ethmoidal and mandibular defects. They all had cerebro-spinal fluid leak (CSF) and recurrent meningitis (range from 3 to 7). Two of those patients had sequelae including deafness, paralysis and epilepsy. VT patients (2 patients) all had temporal, occipital bone and cervical vertebrae defects. None had CSF leaks but both died from medullar compression (preceded by tetraparesis in one case). Overall, five out of six patients had type I Chiari malformation. Interferon seemed to be the most efficient medical treatment. Surgery included petrectomy, endonasal surgery for CSF leak management and neurosurgery for medullar management but could not guarantee long-term effects. CONCLUSION: Main issues in skull base defects are CSF leaks and medullar compressions. Surgical treatment is necessary in both cases but can only be satisfactory if general medical treatment can stabilise the disease.

Decompressive Craniectomy in Children with Severe Traumatic Brain Injury: A Multicenter Retrospective Study and Literature Review.

BACKGROUND: Severe traumatic brain injury (TBI) is the most common cause of disability in children. Refractory increased intracranial pressure can be a therapeutic challenge. Decompressive craniectomy can be proposed when medical management is insufficient, but its place is not clearly defined in guidelines. The aim of this study was to identify prognostic factors in children with TBI. METHODS: We performed a retrospective, multicenter study to analyze long-term outcomes of 150 children with severe TBI treated by decompressive craniectomy and to identify prognostic factors. RESULTS: A satisfactory neurologic evolution (represented by a King's Outcome Scale for Childhood Head Injury score >3) was observed in 62% of children with a mean follow-up of 3.5 years. Mortality rate was 17%. Prognostic factors associated with outcome were age, initial Glasgow Coma Scale score, presence of mydriasis, neuromonitoring values (maximal intracranial pressure >30 mm Hg), and radiologic findings (Rotterdam score ≥4). CONCLUSIONS: This study in a large population confirms that children with severe TBI treated by decompressive craniectomy can achieve a good neurologic outcome. Further studies are needed to clarify the use of this surgery in the management of children with severe TBI.